The present disclosure generally relates to methods for producing opioid derivatives. More particularly, the present disclosure relates to the preparation of hydromorphone, hydrocodone, or a derivative thereof, by means of a non-catalytic hydrogenation reaction of thebaine, oripavine or a derivative thereof, respectively, using a hydrazide reagent, followed by hydrolysis of the hydrogenated intermediate at a low temperature and for a short period of time. Additionally, the present disclosure relates to a composition comprising the desired hydromorphone, hydrocodone, or a derivative thereof, in combination with a 6-beta compound that is structurally related thereto.
Hydrocodone and hydromorphone are opiate analgesics having similar properties to codeine and morphine. The development of new opiate derivatives are desirable as potential sources of new analgesics. Conventional methods for producing hydrocodone and hydromorphone typically involve a two or three step process, involving reductions/oxidations, usually from morphine or codeine. Unfortunately, the latter methods can be expensive and inefficient.
Attempts to improve efficiency have included the use of catalytic methods. Known catalytic methods include the use of metallic catalysts or complexes, deposited on a support of some kind (e.g., an activated carbon support). However, the preparation of the catalysts can be difficult and yields are often poor, and isolation of the product is often burdensome. Furthermore, morphine and codeine are themselves intrinsically valuable analgesics and their use as reaction starting compounds limits them from being used for medicinal purposes in their own right.
Known catalytic methods, including the use of finely-divided platinum or palladium in an acidic media, can be environmentally undesirable. Enzymatic methods of conversion have also been attempted. However, like many of the catalysts discussed above, they can be costly and difficult to scale up.
Accordingly, a need continues to exist for improved methods for producing various opioids, including hydrocodone, hydromorphone, and derivatives thereof. Desirably, such methods would not require use of heterogeneous or homogeneous metal catalysts and/or would not utilize morphine or codeine as starting compounds.